Iulia Gabriela Cresneac

Protein misfolding and aggregation represent key pathological mechanisms in neurodegenerative and systemic amyloid disorders, yet disease-modifying therapeutic strategies remain limited. In recent years, plant-derived nanomaterials have attracted increasing attention as multifunctional platforms capable of interacting with misfolded proteins and modulating aggregation-related pathways. This review examines the evolution of research between 2015 and 2025 on plant-derived nanomaterials—including green-synthesized metallic nanoparticles, plant extracellular vesicles, and phytochemical-based nano-delivery systems—in the context of protein misfolding disorders. The available literature was analyzed to identify principal mechanisms of action, experimental models, and emerging therapeutic perspectives. Current evidence suggests that these nanomaterials may influence protein aggregation through direct molecular interactions, modulation of oxidative stress and neuroinflammatory responses, and enhancement of cellular protein clearance processes. However, the field remains characterized by methodological heterogeneity, limited standardization, and insufficient translational validation. By synthesizing recent developments, this review highlights key research trends, mechanistic gaps, and future directions necessary for advancing plant-derived nanomaterials toward biomedical applications targeting protein misfolding diseases.

Background: Polyphenols—bioactive compounds abundant in plant-based foods—are increasingly recognised for their capacity to modulate the gut microbiota. As the gut microbiome plays a central role in metabolic regulation, immune function, and disease prevention, understanding how specific polyphenol subclasses influence microbial diversity and functionality remains essential. Despite growing evidence of their benefits, the precise effects of flavonoids, phenolic acids, and anthocyanins on gut microbial composition are not yet fully clarified. Objective: This study aimed to evaluate the impact of dietary polyphenols on gut microbiota composition and function, with a particular focus on the abundance of Bifidobacterium, a key beneficial genus associated with metabolic and immune health. It was hypothesised that polyphenol-rich interventions were associated with increases in Bifidobacterium abundance and enhance overall microbial diversity. Design: A systematic review and meta-analysis were conducted following PRISMA guidelines. Human intervention studies published between January 2015 and February 2025 were retrieved from PubMed, Scopus, and Web of Science. A predefined PICO framework guided study selection. Twenty-two studies were synthesised using thematic analysis, and four of these were eligible for quantitative meta-analysis. The meta-analysis was performed in R (version 4.4.1) using the metafor and meta packages, calculating standardised mean differences (SMD) under a random-effects model to account for heterogeneity. Extracted data included study design, population characteristics, polyphenol subclass, intervention type, microbiome assessment method, and key outcomes. Results: Across the 22 reviewed studies, polyphenols—particularly flavonoids and phenolic acids from foods such as berries, grape pomace, and green tea—consistently increased beneficial microbial taxa including Bifidobacterium, Faecalibacterium, and Lactobacillus. These microbial shifts were associated with improved metabolic markers, reduced inflammation, and enhancements in gut barrier integrity. Polyphenol-rich dietary patterns also showed benefits in conditions such as NAFLD, prediabetes, and depression. However, findings were influenced by interindividual variability, short intervention durations, and inconsistent methodologies. The meta-analysis revealed a significant positive effect of polyphenol intake on Bifidobacterium abundance (SMD = 0.81; 95% CI: 0.18–1.44; p = 0.0114), corresponding to a moderate-to-large effect size. Substantial heterogeneity (I² = 77.4%) suggested considerable variation in intervention types, dosage, study design, and microbiome analysis methods. Conclusions: Polyphenol-rich diets were associated with increased Bifidobacterium abundance and favourable modulation of gut microbiota composition, supporting their potential as a nutritional strategy to enhance gut and metabolic health. However, interstudy variability highlights the need for more standardised, long-term, and mechanistically focused human trials. Future research should incorporate multi-omics approaches, personalised nutrition frameworks, and consistent microbiome analysis methods to better understand the pathways linking polyphenol intake and host health outcomes.